This laboratory has had a longstanding interest in the origins and pathophysiological implications of the early-labeled peak of bile pigment. Currently, emphasis is being placed on rapidly labeled heme fractions which we have recently observed in both of the major sites of heme synthesis, young erythroid cells and the liver, and which may be important regulators of both heme and protein synthesis. The nature and biological significance of these labile heme fractions will be studied by attention to: the relationship between this heme fraction in erythroid cells to the synthesis of globin and a major non-heme protein, carbonic anhydrase; the role of early-labeled heme synthesis in the development of hemoglobin formation and erythroid cell differentiation; the possible association of the early heme fraction in hepatic cells to major liver hemoproteins such as cytochrome P450, as opposed to the possibility that it represents a labile pool of unassigned heme; biochemical characterization of the heme compounds comprising the different phases of early heme synthesis in the liver; and the possible role of erythropoietin in reducing early heme synthesis in the liver as it stimulates hemoglobin synthesis in the bone marrow. Other studies will be concerned with the metabolism of iron in liver cells in vitro as an alternative approach to the investigation of rapid heme turnover in this tissue.